Gallbladder Dyskinesia: When to Operate?

Gall bladder dyskinesia is a clinical condition, refers to presence of biliary pain in absence of gallstones. Current evaluation and management of this condition is controversial. This article explores the current evidence available in the evaluation and treatment of such patients with emphasis on selection of patients who would benefit from cholecystectomy. gallbladder


INTRODUCTION
Gall Bladder dyskinesia also Known as chronic cholecystitis, Cystic duct syndrome, Gall bladder spasm or Functional gall bladder disorder. It is a clinical entity that refers to presence of right upper quadarant pain or symptoms of biliary colic in the absence of gallstones or sludge [1].
The true prevalence of gall bladder dyskinesia (GBD) is largely unknown. A large epidemiological study estimated the prevalence of biliary pain in absence of gallstone to be about 2.4% [2]. An Italian study, which used ultrasound screening, found biliary pain without gallstone in 7.6% of men and about 20.7% of women [3,4].
Pathogenesis of gall bladder dyskinesia is unclear, but it is generally regarded as a gall bladder motility disorder. It may result from an initial metabolic disorder such as bile supersaturation or a primary motility disorder in the

CCK-CS
This test is used to estimate the Gall bladder ejection fraction (GBEF). Patient's with GBEF less than 35% to 40% are considered to have GBD and are more likely to respond to cholecystectomy [10,11].
Cholecystokinin (CCK) is a polypeptide secreted from the duodenal mucosa in response to meals especially fatty meal. It has numerous effects including contraction of gall bladder, relaxation of sphincter of Oddi, contraction of pylorus, inhibition of gastric emptying and relaxation of lower esophageal sphincter. It also stimulates secretion of hepatic bile and pancreatic enzyme.
The current definition of what constitute an abnormal GBEF is based on a small study of 40 asymptomatic volunteers who underwent CCK-CS. The mean ejection fraction was 74.5% +/-12.2% and the pathologic ejection fraction was arbitrarily set at 40% (3 standard deviation below the mean) [12]. There is a considerable variability in the literature regarding the optimal technique.

Box 1. Rome III criteria for gall bladder dyskinesia
Recurrent right upper quadrant or epigastric pain and all of the following:  Pain last for 30 minutes or longer.  Pain builds up to a steady state.  Pain is severe enough to interrupt patient's daily activity or leads to an emergency department visit.  Pain is not relieved by bowel movement, postural change, or antacids.  Other conditions that would explain the symptoms are excluded.

Supportive Criteria:
Pain with one or more of the following: Nausea and vomiting, radiation to back or right sub-Scapular area, awakening from deep sleep due to pain.
Functional Gall bladder disorder:  Fulfill above criteria  Gall bladder present  Normal Liver enzyme, Bilirubin and amylase/lipase.
The variability exist whether Sinclide (CCKanalogue) or fatty meal was used, how much and how long it was infused. A standard technique include an overnight fast followed by intravenous injection of either 99mTC-diisopropyliminodiacetic acid (DISIDA) or 99mTc hepatic iminodiacetic acid (HIDA). The radio labeled tracer is excreted in the bile and flows in to the gall bladder. After 45-90 minutes baseline radioactivity is measured over gall bladder. A slow infusion of CCK is started (Sinclide 0.02 mg/Kg given over 30-60 minutes) [13]. This will stimulate gall bladder contraction leading to expulsion of the radiolabeled tracer. Following infusion of CCK radioactivity over gall bladder area is again measured and subtracted from base line activity.
Rapid infusion of CCK causes cramps and patients discomfort and gives highly variable results [10]. Slower infusion rate leads to less inter and intra subject variability and overall increases the mean GBEF compared to rapid infusion [14,15,16].

ROLE OF CHOLECYSTECTOMY IN GBD
A systematic review [17]  , included only one trial with 21 patients randomized 11 to cholecystectomy and 10 to control. All patients in the cholecystectomy group and only one patient in the control group had symptomatic improvement in symptoms (P= 0.0001) after a mean follow up period of 33.6 months. The reviewers concluded that the evidence of effectiveness of cholecystectomy in GBD is based on a single small trial at risk of bias. They recommended further good quality randomized control trials to confirm or reject the promising result.
Dave RV et al.
[21] conducted a retrospective outcome study following laparoscopic cholecystectomy involving 100 patients with suspected GBD and positive CCK-CS (GBEF < 35%) with a median follow up of 12 months. They reported that 84% of the patients have symptomatic improvement and 52% have no residual pain. They concluded that a positive CCK-CS test is a useful functional diagnostic tool in patients with suspected GBD, with favorable outcome following surgery.

CONCLUSION
Symptomatic relief after laparoscopic cholecystectomy for gall stone disease is between 85% and 90%. The data for biliary dyskinesia is not as good and are of poor quality. They suggest that 65% to 70% of patients will be cured and 20% to 30% will improve with cholecystectomy. In patients with acalculous biliary pain approximately 60% to 80% will have abnormal GBEF on CCK-HIDA [22].
The patients with suspected biliary dyskinesia, which fulfills Rome III criteria, should undergo CCK stimulated cholescintigraphy. Those who have GBEF less than 35% to 40% should be offered cholecystectomy. Patients who have typical symptoms with GBEF greater than 40% present a challenge. They should be placed on a conservative treatment with symptomatic relief and observed for a period of time. The recommendation for cholecystectomy should be made on case-to-case basis with a frank and open discussion about limitation of our understanding of this disease process.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.